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Dasatinib dose reduction not going quite to plan

I've been reducing dasatinib dose for some time - from 100, to 70, to 50 and finally to 20. There's been a few months and a few PCR tests between each change. 

My first PCR on 20mg of dasatinib was taken 6 weeks after commencing that dose and was a very good 0.002% IS. 6 weeks later, it's jumped a log and it's 0.025%. 

Still MMR, but clearly was only a touch from MR5 only a few weeks ago so it's not really gone to plan. 

Nothing changes yet. I'll continue at 20mg for another 4 weeks and test again. Perhaps the PCR might just bumble around that level which would be fine. Maybe it'll drop, maybe it'll increase another log. Who knows. 

I was definitely feeling better at a low dose so fingers crossed it doesn't fly up.

Plenty to be hopeful for and while I might have a glass of wine or two and commiserate tonight, I'm not going to get worried or let it stress me out too much. 

David. 

 

David,

My fingers are crossed for you! Lower dose is so much better for overall side effects management.

A few thoughts:

1. Are you supplementing with Curcumin.

Significant research is 'hinting' that Curcumin down regulates genes necessary for leukemia proliferation. Not a cure, but may enable you to take lower dose and it be just as effective. I take 2 grams of C3 Curcumin with bioperine (pepper) per day, but when I was at a much higher PCR level, I took as much as six - eight grams per day. I still take 4 grams from time to time spread throughout the day. Curcumin impact on CML is dose dependent so more is better up to around 10 grams per day. One case where more is better. I would take more myself, but C3 is pricey. Two seems to keep me where I am.

https://www.ncbi.nlm.nih.gov/pubmed/26116834

https://www.nature.com/articles/s41598-018-20179-6

2. Are you taking vitamin D3

Vitamin D (which is made by the body from D3 that is ingested) is vital for immune system health including activation of T-cells which attack cancers. Evidence is emerging that high normal vitamin D levels (> 50ng/ml) activates genes which cause leukemia cell apoptosis. Not a cure, just slows down expansion of leukemia and may actually stop it growing. In combination with your low dose dasatinib, may just be the trick to get you back down again.

Keep in mind that you have plenty of time to experiment (i.e. chronic phase; no blasts) so if you have to increase dose, you can do so incrementally (e.g. 40 mg). But I do hope you regain trend down by considering the above.

https://www.curetoday.com/articles/curcumin-and-vitamin-d-treatment-may-...

(could try fasting too!)

 

 

David:

We'll all be praying that it's just a blip.  I had a blip up from undetected to <.003% about 6 months after I reduced nilotinib dose from 300 to 150 mg/day, but I have stayed at <.003% for a year now since then.  Here's hoping that your next test either stays the same or that you get that other zero back.  I think we all understand the anxiety roller-coaster around test time and that's why we've got this forum.  Hang in there and try to stay positive.

Yes, supplementing with both.

But I will be honest. I have not been massively compliant with things other than dasatinib. I have never missed a TKI dose in over 6 years, but with the arrival of my twin girls (8 months old, extremely pre-term so 5 months corrected) I have not been taking my supplements as often as I should.

This evening I have refilled my pill boxes, so the next few weeks will be different.

Scuba: you are good on supplements. I have a "Organic turmeric, with bioperine". 500mg. Maybe not the right thing? The D3 is 10,000 IU - this one.

David.

David,

The D3 is plenty. You should still have a blood test to know your level.

And of course, if you don't take the supplement, it doesn't do any good (smile).

On Curcumin. I'm not sure if this is a turmeric supplement or a true Curcumin. I suspect it is Curcumin because Bioperine is licensed by Sabinsa.

In that case, 500 mg is one pill and you would need to take 4 of these to equal my dose. You need two grams MINIMUM.

I have a suspicion, however, that your PCR test is an anomaly. We'll see. You'll be fine. Stay vigilant.

hey, david! i'm sorry about your last result, but as you also know, the test is not that reliable and you're right to wait for the next result. I remember when emma was lowering her dose for the first time and she had big bounces like that until things got more stable. Many others have big bounces even if they're not lowering their doses (like chris and me!). But, if you lose MMR i think it's better to restart at full dose (100mg) and then lower dose after things settle down, just to stay on the safe side. Good luck, buddy!

David - Very familiar with what you must be feeling - I think we all are - and commiserate with you.  On 20 mg Sprycel myself, I'm always waiting for the other shoe to drop.  Things go along pretty smoothly for awhile and we get used to our new normal, and then - bang - we're reminded of what is actually in control of us.  But, you have the right attitude, you're still safe, and the odds are on your side that it's a test-related bounce and not a harbinger of doom. I know you will keep your mind occupied before the re-test.  I like to establish a spectrum of worst-case (and what I would do about that) to best-case in my mind and then try to stop thinking about it.  Somehow, that makes me feel more prepared and in control. Keep us posted. 

Thanks!

My silver lining thought for the day was that I forgot to apply the IS correction to my results.

The Barts lab coversion factor is a rather handy 0.5 - so on IS I've gone from 0.001% to 0.0125% which though it's still a full log, it's pretty much still MR4.

David

Oh yes, that's much better!

I'm on a 6 weekly PCR schedule at the moment because of dose reductions. The last one showed a full log increase to MR4, so obviously the concern was that 20mg of dasatinib was just not enough and that another log increase or two was on the cards. 

I just got my latest results in, and it's held stable at MR4. So while my numbers are up from the MR5 level they had been a stable MR4 would be more than acceptable. 

A couple of pints are in order this evening! 🎉

That's great news David.  I remember my 3 rather quick dose reductions in succession from 600 - 450 - 300 - 150 mg nilotinib. I too was tested every six weeks during this approx 9 month stretch in 2017.  On one of the tests during that stretch, I went from negative to <.003%; after some worry, I realized that the 2 results were essentially the same.  I have held at that result for a bit over a year now and am on 6 month testing.  Here's hoping that you have the same experience.  I know you'll be happy if you can hold steady at MR4 on 20 mg dose.  Continued good luck 

... only a couple of pints? You earned more than that.

Nice bit of reassurance today that 20mg of dasatinib seems to be doing its thing. Though I’d rapidly gone up a log when going from 50 to 20mg, it was only from MR5 to MR4. Today I’m at 0.005% (IS), from a sample of > 110,000 assays so closer to MR4.5 than MR4. But more importantly it’s another couple of months without another rise. Really pleased with that, I’ve definitely been feeling better on 20mg than any other of the higher doses ... I’m somehow managing to hold together the twins and a busy time at work which I’m pretty sure I would not have done so well at on a higher dose.

Doctor today (not my usual one, only 3rd appointment in 6 years without her!) was asking about my TFR appetite. One day, for sure ... but I think I’m going to wait a while yet. The last 12 months have been a roller-coaster so I think I’ll stick rather than twist for the time being.

I’ve always been happy with how my hospital manage dose reductions. I’ll now go back to 3-monthly clinics given a bit of stability, but stay on 6 weekly PCR tests.

You are going to do fine on 20 mg ! Looking forward to the day when your lab reports 'undetected'.

Of course, you do know that "undetected" and "0.005" are indistinguishable. Anything less than 0.01% is noise.

Next stop ..... Treatment Free Remission. (That's my goal as well)

I don’t trust “undetected”. I’d much prefer to see 0.001-0.005% than that. And I hope my and others lab’s tech improves over time that eventually we’ll start to see undetected turn into MR6.

Some years back I had an “undetected” result, with the one before and after somewhere between MR3 and 4. I’m sure it was a clerical error and someone else’s blood was tested. 

So I often tell people not to worry about blips, because that’s usually all they are. But you still can’t help but worry.

Looking back 18 months, and at a log rise after a drop to 20mg of dasatinib I was a little (honestly, just a little - not freaking out) worried that my dose reduction plan wasn’t going to plan.

Since then, I’ve hovered around MR4 to MR5 which has been fantastic. Very happy with that.

My latest PCR test was undetectable, on more than 180,000 assays. Great news for me, but I’m not getting excited - the next one might be a little higher. As I explained it to my wife (who was much happier about it than me!) is that I shouldn’t worry when the numbers go up a bit, so equally I shouldn’t be too happy when they go down a bit. 

Rudyard Kipling had it right, “treat those two impostors just the same” for both the ups and the downs.

David.

Imagine that, David - you lowered dasatinib dose and CML went undetected!

As you pointed out, no reason to get excited - but yes - get excited.

I have long suspected lower dose lets immune response increase without lowering drug action. You are in a sweet place.

Just an FYI - I am at 10 mg now - and am still undetected. I am getting ready to stop altogether at next test. Just have to build up some supply.

(To be honest - I skip a lot of days now. I just don't think about it anymore. I probably missed half my doses at last checkup and I was still 'undetected'. I restarted on and off because of mild withdrawal symptoms)

I presume you just chop the 20mg in two?

I’d be rubbish at missing doses! I stick to my treatment plan ... I have never, ever missed a dose. 

My doctor is keen-ish to talk about discontinuing, but I am quite happy where I am. The last thing I need right now is too rock the boat, young kids and all. 
 

David. 

I so understand the psychology of CML - (and Covid for that matter).

But the reality for you (and many of us) is that CML is in our rear view mirror once cytogenetic remission is achieved.

I either cut the 20 mg pill in half (I have a precision cutter) or I just take 20 mg. every other day. As it turns out, M.D. Anderson now has a study on every other day dosing. Mostly to help patients overcome pleural effusion without losing response. There is a correlation in patients who develop pleural effusion also achieving dramatic response to dasatinib - but only if they can keep taking the drug.

Great news David,

I think once anyone reaches MMR3 anything further below is inconsequential if you’re not interested in TFR. With that said the lower the better obviously provides greater protection and the option of TFR if that’s what you want.

I often recite your notion of not getting too excited when down and not too worried when up. But I think in your case you should celebrate your recent drop. This thing is a rollercoaster but I say celebrate the wins and forget the loses (as best you can because that is a worry not matter how much we convince ourselves otherwise)

Alex

My doc uses the analogy that "the difference between <0.003 and 0.000 is the distance between the front side of a piece of typing paper and the back side". I'm sure it can be measured, but who cares?

 

My dr has me on 50 mg. My last Count was .0055.   Hoping to get down to 20 mg after my next labs in Feb.    I asked him about every other day and he said maybe in feb

Forwarding an article about lowering Nilotinib dose.

https://undark.org/2020/12/09/cancer-drugs-less-might-be-more/

Hello David,

Sorry this is a bit off post! I see that you are admin to the facebook group, which I have applied to join. Does approval take very long?

All the best

David

It usually doesn’t take long - depends on when  one of the admin’s get around to it!

I’ve just approved you. 

David. 

My BCR/ABL also went up when I dropped from 50 to 20, but then started going back down.

11/13/2020 - 0.0345
8/10/2020  - 0.0671
4/27/2020  - 0.0793
2/10/2019  - 0.0243  went from dasatinib 50 to 20 on this date.
11/18/2019 - 0.0800   dasatinib 50
10/7/2019 - 0.2933  dasatinib 100 (a nightmare for me)